A member of the class I viral membrane fusion proteins, the coronavirus spike consists of three segments-an ectodomain, a single-pass transmembrane anchor, and a short intracellular tail. The ectodomain can be divided into a receptor binding S1 subunit and a membrane -fusion S2 subunit. The amino acid sequences of S1 diverge across different genera but are relatively conserved within each genus. S1 contains two independent domains, a N-terminal domain (S1-NTD) and a C-terminal domain (S1-CTD, also called S1 C-domain). Either or both of these S1 domains can function as a receptor-binding domain (RBD).